Surgery and Experimental Medicine
Surgery and Experimental Medicine
Fonseca A.C.R.G.,University of Coimbra |
Moreira P.I.,University of Coimbra |
Oliveira C.R.,University of Coimbra |
Cardoso S.M.,University of Coimbra |
And 2 more authors.
Molecular Neurobiology | Year: 2015
In Alzheimer’s disease, the accumulation of amyloid-beta (Aβ) in the brain occurs in the parenchyma and cerebrovasculature. Several evidences support that the neuronal demise is potentiated by vascular alterations in the early stages of the disease, but the mechanisms responsible for the dysfunction of brain endothelial cells that underlie these cerebrovascular changes are unknown. Using rat brain microvascular endothelial cells, we found that short-term treatment with a toxic dose of Aβ1-40 inhibits the Ca2+ refill and retention ability of the endoplasmic reticulum and enhances the mitochondrial and cytosolic response to adenosine triphosphate (ATP)-stimulated endoplasmic reticulum Ca2+ release. Upon prolonged Aβ1-40 exposure, Ca2+ homeostasis was restored concomitantly with a decrease in the levels of proteins involved in its regulation operating at the plasma membrane, endoplasmic reticulum, and mitochondria. Along with perturbations in Ca2+ regulation, an early increase in the levels of oxidants and a decrease in the ratio between reduced and oxidized glutathione were observed in Aβ1-40-treated endothelial cells. Under these conditions, the nuclear levels of oxidative stress-related transcription factors, namely, hypoxia-inducible factor 1α and nuclear factor (erythroid-derived 2)-related factor 2, were enhanced as well as the protein levels of target genes. In conclusion, Aβ1-40 affects several mechanisms involved in Ca2+ homeostasis and impairs the redox homeostasis simultaneously with stimulation of protective stress responses in brain endothelial cells. However, the imbalance between cell death and survival pathways leads to endothelial dysfunction that in turn contributes to cerebrovascular impairment in Alzheimer’s disease. © 2014, Springer Science+Business Media New York.
PubMed | Surgery and Experimental Medicine, Academic Unit of Obstetrics and Gynecology and Italian National Cancer Institute
Type: | Journal: European journal of obstetrics, gynecology, and reproductive biology | Year: 2016
To investigate the impact of hematologic toxicity and leukopenia in locally advanced cervical cancer patients undergoing neoadjuvant chemotherapy (NACT).Data of consecutive patients undergoing platinum-based NACT followed by surgery were retrospectively searched in order to evaluate the impact of chemotherapy-related toxicity on survival outcomes. Toxicity was graded per the Common Terminology Criteria for Adverse Events (CTCAEv.4.03). Survival outcomes were evaluated using Kaplan-Meir and Cox hazard models.Overall, 126 patients were included. Among those, 94 (74.6%) patients experienced grade2+ hematologic toxicity; while, grade2+ non-hematologic toxicity occurred in 11 (8.7%) patients. After a median follow-up of 37.1 (inter-quartile range, 12-57.5) months, 21 (16.6%) patients experienced recurrence. Via multivariate analysis, no factor was independently associated with disease-free survival; while a trend toward worse prognosis was observed for patients experiencing grade2+ leukopenia at cycle-3 (HR:3.13 (95%CI: 0.94, 10.3); p=0.06). Similarly, grade2+ leukopenia (HR:9.98 (95%CI: 1.14, 86.6); p=0.03), lymph-node positivity (HR:14.6 (95%CI:1.0, 214.4); p=0.05) and vaginal involvement (HR:5.81 (95%CI:1.43, 23.6); p=0.01) impacted on overall survival, at multivariate analysis. Magnitude of leukopenia correlated with survival (p<0.001).Although, our data have to be confirmed by prospective investigations, the present study shows an association between the occurrence of leukopenia and survival outcomes. NACT-related immunosuppression might reduce the response against the tumor, thus promoting cancer progression.
Veronesi F.,Rizzoli Orthopaedic Institute |
Torricelli P.,Rizzoli Orthopaedic Institute |
Giavaresi G.,Rizzoli Orthopaedic Institute |
Sartori M.,Rizzoli Orthopaedic Institute |
And 5 more authors.
Journal of Orthopaedic Research | Year: 2014
Osteoarthritis (OA) is a joint pathology characterized by fibrillation, reduced cartilage thickness and subchondral bone sclerosis. There is evidence that pulsed electromagnetic fields (PEMFs) counteract OA progression, but the effect of two different PEMF frequencies has not yet been shown. The aim of this study was to test the effectiveness of PEMFs at two different frequencies (37 and 75 Hz) in a late OA stage in 21-month-old Guinea pigs. After 3 months of 6 h/day PEMF stimulation, histological and histomorphometric analyses of the knees were performed. At both frequencies, PEMFs significantly reduced histological cartilage score, fibrillation index (FI), subchondral bone thickness (SBT) and trabecular number (Tb.N) and increased trabecular thickness (Tb.Th) and separation (Tb.Sp) in comparison to the not treated SHAM group. However, PEMFs at 75 Hz produced significantly more beneficial effects on the histological score and FI than 37 Hz PEMFs. At 75 Hz, PEMFs counteracted cartilage thinning as demonstrated by a significantly higher cartilage thickness values than either those of the SHAM or 37 Hz PEMF-treated groups. Although in severe OA both PEMF frequencies were able to limit its progression, 75 Hz PEMF stimulation achieved the better results. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
Nappi L.,University of Foggia |
Pontis A.,Hospital San Francesco |
Sorrentino F.,University of Foggia |
Greco P.,Surgery and Experimental Medicine |
Angioni S.,University of Cagliari
European Journal of Obstetrics Gynecology and Reproductive Biology | Year: 2016
Objective To evaluate the feasibility and safety of office hysteroscopic metroplasty using a 980 nm diode laser. Study design 18 patients were treated for septate uterus between 2013 and 2016. The indications for hysteroscopic metroplasty were recurrent abortion in 11 of the women and primary infertility in the other seven. We used a 5 mm-office hysteroscope with a diode laser fibre. After exploration of the cavity, the septum was divided with use of the laser fibre. Results Operating time was 13,16 ± 1,33 min. Intraoperative pain was 3,05 ± 0,72. No intraoperative or postoperative complications were observed. Follow-up performed 2 months after the hysteroscopic metroplasty confirmed the complete removal of the septum and no evidence of intrauterine synechiae. Conclusion Office hysteroscopic metroplasty with use of a diode laser is safe and feasible; we believe that vaporization of the septum with a diode laser could reduce the formation of adhesions and consequently reduce the occurrence of septum persistence. © 2016 Elsevier Ireland Ltd
PubMed | University of Foggia, Hospital San Francesco, University of Cagliari and Surgery and Experimental Medicine
Type: | Journal: European journal of obstetrics, gynecology, and reproductive biology | Year: 2016
To evaluate the feasibility and safety of office hysteroscopic metroplasty using a 980nm diode laser.18 patients were treated for septate uterus between 2013 and 2016. The indications for hysteroscopic metroplasty were recurrent abortion in 11 of the women and primary infertility in the other seven. We used a 5mm-office hysteroscope with a diode laser fibre. After exploration of the cavity, the septum was divided with use of the laser fibre.Operating time was 13,161,33min. Intraoperative pain was 3,050,72. No intraoperative or postoperative complications were observed. Follow-up performed 2 months after the hysteroscopic metroplasty confirmed the complete removal of the septum and no evidence of intrauterine synechiae.Office hysteroscopic metroplasty with use of a diode laser is safe and feasible; we believe that vaporization of the septum with a diode laser could reduce the formation of adhesions and consequently reduce the occurrence of septum persistence.
Mangolini A.,University of Ferrara |
Bonon A.,University of Ferrara |
Volinia S.,University of Ferrara |
Lanza G.,Surgery and Experimental Medicine |
And 6 more authors.
FEBS Open Bio | Year: 2014
Renal cell carcinoma is a common neoplasia of the adult kidney that accounts for about 3% of adult malignancies. Clear cell renal carcinoma is the most frequent subtype of kidney cancer and 20-40% of patients develop metastases. The absence of appropriate biomarkers complicates diagnosis and prognosis of this disease. In this regard, small noncoding RNAs (microRNAs), which are mutated in several neoplastic diseases including kidney carcinoma, may be optimal candidates as biomarkers for diagnosis and prognosis of this kind of cancer. Here we show that patients with clear cell kidney carcinoma that express low levels of miR501-5p exhibited a good prognosis compared with patients with unchanged or high levels of this microRNA. Consistently, in kidney carcinoma cells the downregulation of miR501-5p induced an increased caspase-3 activity, p53 expression as well as decreased mTOR activation, leading to stimulation of the apoptotic pathway. Conversely, miR501-5p upregulation enhanced the activity of mTOR and promoted both cell proliferation and survival. These biological processes occurred through p53 inactivation by proteasome degradation in a mechanism involving MDM2-mediated p53 ubiquitination. Our results support a role for miR501-5p in balancing apoptosis and cell survival in clear cell renal carcinoma. In particular, the downregulation of microRNA501-5p promotes a good prognosis, while its upregulation contributes to a poor prognosis, in particular, if associated with p53 and MDM2 overexpression and mTOR activation. Thus, the expression of miR501-5p is a possible biomarker for the prognosis of clear cell renal carcinoma. © 2014 The Authors.
Comar M.,University of Trieste |
Comar M.,Institute for Maternal and Child Health IRCCS Burlo Garofolo |
Wong C.,Baylor College of Medicine |
Tognon M.,Surgery and Experimental Medicine |
Butel J.S.,Baylor College of Medicine
PLoS ONE | Year: 2014
Objective: Polyomavirus simian virus 40 (SV40) sequences have been detected in various human specimens and SV40 antibodies have been found in human sera from both healthy individuals and cancer patients. This study analyzed serum samples from healthy pregnant women as well as cord blood samples to determine the prevalence of SV40 antibodies in pregnancy. Copyright:Methods: Serum samples were collected at the time of delivery from two groups of pregnant women as well as cord bloods from one group. The women were born between 1967 and 1993. Samples were assayed by two different serological methods, one group by neutralization of viral infectivity and the other by indirect ELISA employing specific SV40 mimotopes as antigens. Viral DNA assays by real-time polymerase chain reaction were carried out on blood samples.Results: Neutralization and ELISA tests indicated that the pregnant women were SV40 antibody-positive with overall prevalences of 10.6% (13/123) and 12.7% (14/110), respectively. SV40 neutralizing antibodies were detected in a low number of cord blood samples. Antibody titers were generally low. No viral DNA was detected in either maternal or cord bloods.Conclusions: SV40-specific serum antibodies were detected in pregnant women at the time of delivery and in cord bloods. There was no evidence of transplacental transmission of SV40. These data indicate that SV40 is circulating at a low prevalence in the northern Italian population long after the use of contaminated vaccines. © 2014 Comar et al.
PubMed | Laboratories of Cell Biology and Molecular Genetics, University of Ferrara and Surgery and Experimental Medicine
Type: | Journal: Journal of cellular physiology | Year: 2016
The human JC polyomavirus (JCPyV) is an ubiquitous viral agent infecting approximately 60% of humans. Recently, JCPyV sequences have been detected in semen samples. The aim of this investigation was to test whether semen JCPyV genotyping can be employed to trace the origin continent of males. Semen DNA samples (n=170) from males of different Continents were investigated by PCR for the polymorphic JCPyV viral capsid protein 1 (VP1) sequences, followed by DNA sequencing. JCPyV sequences were detected with an overall prevalence of 27.6% (47/170). DNA sequencing revealed that European males carried JCPyV types 1A (71.4%), 4 (11.4%), 2B (2.9%), 2D1 (2.9%), and 3A (2.9%). Asians JCPyV type 2D1 (66.7%) and Africans JCPyV types 3A (33.3%) and 1A (33.3%). In 10.6% of males, two different JCPyV genotypes were detected, suggesting that the second JCPyV genotype was acquired in the destination country. This study indicates that the majority of semen samples found to be JCPyV-positive, were infected with the JCPyV genotype found in the geographic area of male origin. Therefore, semen JCPyV genotyping could be employed to trace the origin continent of males. Our findings could be applied to forensic investigations, in case of for instance sexual crimes. Indeed, JCPyV genotyping should enable investigators to make additional detailed profiling of the offender. J. Cell. Physiol. 9999: 1-4, 2016. 2016 Wiley Periodicals, Inc.
Graziano A.,Surgery and Experimental Medicine |
Caserta D.,Surgery and Experimental Medicine |
Piva I.,Surgery and Experimental Medicine |
Lo Monte G.,Surgery and Experimental Medicine |
And 4 more authors.
European Review for Medical and Pharmacological Sciences | Year: 2013
AIM: This prospective study was designed to assess whether the use of GnRH antagonists can improve the success rate of controlled ovarian stimulation (COS) in intrauterine insemination (IUI) treatments. PATIENTS AND METHODS: Eighty patients were divided into two groups: GnRH antagonist group (Group A, n=40) and control group (Group B, n=40). Patients in Group B underwent COS with recombinant Follicle Stimulating Hormone (r-FSH, 50-75 IU/d) only, while patients in Group A were administered r-FSH (50-75 IU/d) plus cetrorelix (0.25 mg/d, starting when ≥ 2 follicles ≥ 14 mm were detected on ultrasound scan). In both groups a single insemination was performed 36 hours after human Chorionic Gonadotropin (hCG, 250 mcg) administration. The primary outcome was clinical Pregnancy Rate (PR). Secondary outcomes were ongoing PR, incidence of Premature Luteinization (PL), number of follicles with mean diameter ≥ 16 mm and between 11 and 15 mm on the day of hCG administration, miscarriage rate, cycle cancellation rate, total amount of r-FSH used and duration of treatment. Student's t test and Chi-square test were used (p < .05 statistically significant). RESULTS: A total of 146 cycles were performed (Group A: n=72; Group B: n=74). A trend towards higher PR in Group A was detected, although it was not statistically significant (Clinical PR: 18.05% vs 10.81%). The number of follicles ≥ 16 mm was significantly increased in Group A. The incidence of both premature LH surge and premature luteinization (PL) was significantly higher in Group B. No significant differences were found in the duration of the stimulation protocol, and in the total amount of r-FSH administered. CONCLUSIONS: The addition of GnRH antagonist in COS/IUI protocol significantly increases the number of mature follicles. However, this multifollicular recruitment is not linked to a significantly higher PR.
Marchi S.,Surgery and Experimental Medicine |
Pinton P.,Surgery and Experimental Medicine
Communicative and Integrative Biology | Year: 2013
Mitochondria receive calcium (Ca2+) signals from endoplasmic reticulum (ER) and decode them into pro-apoptotic inputs, which lead to cell death. Therefore, mitochondrial Ca2+ overload is considered a fundamental trigger of the apoptotic process, and several oncogenes and tumor suppressors modify the activity of protein involvedin Ca2+ homeostasis to control apoptosis. The identification of the channel responsible for mitochondrial Ca2+entry, the Mitochondrial Ca2+Uniporter (MCU), together with its regulatory components, MICU1 and MCUR1, provides new molecular tools to investigate this process. Recent data have also shown that miR-25 decreases mitochondrial Ca2+ uptake through selective MCU downregulation, conferring resistance to apoptotic challenges. MCU appears to be downregulated in human colon cancer samples, and accordingly, miR-25 is aberrantly expressed, indicating the importance of mitochondrial Ca2+ regulation in cancer cell survival. © 2013 Landes Bioscience.